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Over-activation of primate subgenual cingulate cortex enhances the cardiovascular, behavioral and neural responses to threat.

Accepted version
Peer-reviewed

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Type

Article

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Authors

Alexander, Laith 
Sawiak, Stephen J 
Fryer, Tim D 

Abstract

Stress-related disorders such as depression and anxiety are characterized by enhanced negative emotion and physiological dysfunction. Whilst elevated activity within area 25 of the subgenual anterior cingulate cortex (sgACC/25) has been implicated in these illnesses, it is unknown whether this over-activity is causal. By combining targeted intracerebral microinfusions with cardiovascular and behavioral monitoring in marmosets, we show that over-activation of sgACC/25 reduces vagal tone and heart rate variability, alters cortisol dynamics during stress and heightens reactivity to proximal and distal threat. 18F-FDG PET imaging shows these changes are accompanied by altered activity within a network of brain regions including the amygdala, hypothalamus and dorsolateral prefrontal cortex. Ketamine, shown to have rapid antidepressant effects, fails to reverse elevated arousal to distal threat contrary to the beneficial effects we have previously demonstrated on over-activation induced reward blunting, illustrating the symptom-specificity of its actions.

Description

Keywords

Animals, Arousal, Autonomic Pathways, Behavior, Animal, Callithrix, Cardiovascular Physiological Phenomena, Fear, Female, Gyrus Cinguli, Heart Rate, Hydrocortisone, Male, Positron Emission Tomography Computed Tomography

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

11

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Medical Research Council (G1100307)
MRC (1648124)
Wellcome Trust (108089/Z/15/Z)